Identification of Prognostic Markers in Acute Myeloid Leukemia by Using CDNA Microarray PDF Download
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Author: Wei Fang Phang
Publisher:
ISBN:
Category :
Languages : en
Pages : 174
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Book Description
Author: Wei Fang Phang
Publisher:
ISBN:
Category :
Languages : en
Pages : 174
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Book Description
Author: Ingrid Jakobsen
Publisher: Linköping University Electronic Press
ISBN: 9176851958
Category :
Languages : en
Pages : 76
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Book Description
The standard treatment of acute myeloid leukemia (AML) consists of induction chemotherapy, most commonly daunorubicin together with the nucleoside analogue cytarabine (Ara-C), followed by consolidation chemotherapy and in selected cases allogenic stem cell transplantation (allo-SCT). Despite a high initial response rate, a considerable proportion of all AML cases eventually suffer from relapse and the five-year overall survival rate in patients >60 years is only around 15%. Based on cytogenetic analysis, patients are divided into low risk, intermediate risk, and high-risk groups. While low risk patients have a high chance of reaching and remaining in remission after standard induction therapy, high-risk patients are likely to suffer from relapse and should be scheduled for allo-SCT when first complete remission is reached. The intermediate risk group consists of normal karyotype (NK) patients and those with karyotypes of uncertain clinical relevance, but the outcomes are heterogeneous. In NKAML patients, risk classification has improved with the addition of molecular markers including FLT3 internal tandem duplications (ITD) and mutations of NPM1 and CEBPA. Despite this development, there is a group of patients lacking reliable prognostic markers and in some cases the outcomes predicted do not match the outcomes observed, highlighting the need for additional markers. ABCB1 encodes a transporter protein responsible for the extrusion of cytotoxic compounds, including daunorubicin, over the cell membrane, and is a known resistance mechanism. Ara-C is subject to both activating and inactivating metabolic enzymes including DCK (activating), CDA and cN-II (inactivating). ABCB1, DCK, CDA and cN-II are all polymorphic, and SNPs affecting enzyme function and/or activity have potential as prognostic markers. In addition, recurrent IDH1/2 mutations lead to the expression of an enzyme with neomorphic activity associated with epigenetic alterations and disturbed differentiation. Mutations as well as a SNP in codon 105 of IDH1 have prognostic implications in AML, although the effects of different IDH mutations have been unclear. The aim of this thesis was to investigate SNPs in ABCB1 and genes associated with Ara-C metabolism, mutations in IDH1/2 and the IDH1 SNP, and their associations with treatment response and survival in AML. We show that the 1236C>T and 2677G>T SNPs in ABCB1 influence in vitro sensitivity towards AML drugs, with corresponding effects on NK-AML patient survival. These survival differences were seen mainly in patients lacking FLT3-ITD, further adding to the risk stratification. In contrast, the CDA SNPs 79A>C and -451C>T appear to influence survival mainly in FLT3-ITD positive cases. In conclusion, the above-mentioned SNPs have the potential to add important information to risk classifications especially in NK-AML patients with the ambiguous FLT3-ITD-/NPM1- or FLT3-ITD+/NPM1+ genotypes. In addition, we have shown that IDH2 R140 mutation is associated with impaired survival in AML, and that the IDH1 codon 105 SNP appears to confer a worse outcome in a subset of intermediate risk patients without FLT3-ITD. With the introduction of next generation sequencing into clinical diagnostics, IDH mutations may not only provide prognostic information but also guide the selection of patients for new drugs targeting the variant enzyme. Our results indicate that in addition to leukemia-specific mutations, constitutional SNPs may prove useful for further individualizing care-taking and should be considered when implementing these new techniques.
Author: Garden Grove Garden Grove Press
Publisher:
ISBN: 9781544837598
Category :
Languages : en
Pages : 288
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Book Description
This article collection reviews the medical genetics of acute myeloid leukemia and includes 30 papers by various authors. Topics include: Molecular and genetic alterations associated with therapy resistance and relapse of acute myeloid leukemia; Next Generation Sequencing of Acute Myeloid Leukemia: Influencing Prognosis; Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia; Identification of somatic mutations using whole-exome sequencing in Korean patients with acute myeloid leukemia; Clinical implications of genome-wide DNA methylation studies in acute myeloid leukemia; A WIMSical approach to decoding DNA methylation in myeloid leukemia; A three-gene expression-based risk score can refine the European LeukemiaNet AML classification; A de novo acute myeloid leukemia (AML-M4) case with a complex karyotype and yet unreported breakpoints; Acute myeloid leukemia - strategies and challenges for targeting oncogenic Hedgehog/GLI signaling; Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations; Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (UBE2E1) as a prognostic factor in acute myeloid leukemia; The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid leukemia (AML); Homeobox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations; Mutations in the isocitrate dehydrogenase 2 gene and IDH1 SNP 105C > T have a prognostic value in acute myeloid leukemia; Rare MLL-ELL fusion transcripts in childhood acute myeloid leukemia - association with young age and myeloid sarcomas?; Analyzing the gene expression profile of pediatric acute myeloid leukemia with real-time PCR arrays; Computational identification of the normal and perturbed genetic networks involved in myeloid differentiation and acute promyelocytic leukemia; Current findings for recurring mutations in acute myeloid leukemia; Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications; Molecular alterations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes and additional genetic mutations in newly diagnosed acute myeloid leukemia patients; Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics; Long noncoding RNAs: pivotal regulators in acute myeloid leukemia; CYP1A1 MspI polymorphism and acute myeloid leukemia risk: meta-analyses based on 5018 subjects; TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases; A case of acute myeloid leukemia (AML) with an unreported combination of chromosomal abnormalities: gain of isochromosome 5p, tetrasomy 8 and unbalanced translocation der(19)t(17;19)(q23;p13); Hypomethylation and expression of BEX2, IGSF4 and TIMP3 indicative of MLL translocations in Acute Myeloid Leukemia; 5'UTR point substitutions and N-terminal truncating mutations of ANKRD26 in acute myeloid leukemia; Analysis of AML genes in dysregulated molecular networks; SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study; and A novel BCR-ABL1 fusion gene identified by next-generation sequencing in chronic myeloid leukemia. Proceeds from the sale of this book go to the support of an elderly disabled person.
Author: Myriam Marcelle Eyer
Publisher:
ISBN:
Category :
Languages : en
Pages : 88
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Book Description
Author: Hanie Samimi
Publisher:
ISBN:
Category : Acute myeloid leukemia
Languages : en
Pages : 92
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Book Description
Author: Hillard M. Lazarus
Publisher: Springer Science & Business Media
ISBN: 1597454788
Category : Medical
Languages : en
Pages : 885
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Book Description
Since the original publication of Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Allogeneic hematopoietic stem cell transplantation (HSC) has undergone several fast-paced changes. In this second edition, the editors have focused on topics relevant to evolving knowledge in the field in order to better guide clinicians in decision-making and management of their patients, as well as help lead laboratory investigators in new directions emanating from clinical observations. Some of the most respected clinicians and scientists in this discipline have responded to the recent advances in the field by providing state-of-the-art discussions addressing these topics in the second edition. The text covers the scope of human genomic variation, the methods of HLA typing and interpretation of high-resolution HLA results. Comprehensive and up-to-date, Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Second Edition offers concise advice on today's best clinical practice and will be of significant benefit to all clinicians and researchers in allogeneic HSC transplantation.
Author: Simone Mocellin
Publisher: Springer Science & Business Media
ISBN: 038739978X
Category : Medical
Languages : en
Pages : 176
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Book Description
Given the revolutionary implications that the use of this technology might have in the clinical management of cancer patients, the principles of DNA array-based tumor gene profiling must be clearly understood for the data to be correctly interpreted and appreciated. This book, written by leading experts, discusses the technical features characterizing the powerful laboratory tool of microarray technology, and reviews applications in the field of oncology.
Author: Gert-Jan L. Kaspers
Publisher: CRC Press
ISBN: 9783718653874
Category : Medical
Languages : en
Pages : 458
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Book Description
The last ten years have seen the publication of a vast amount of data regarding cellular resistance to drugs in cancer cells. Recent studies have demonstrated that drug resistance assays appear to be predictive of clinical response and suggest that clinicians should now be considering the potential applications of these assays in the treatment of patients with hematological neoplasms. This collection of papers from the International Symposium on the Clinical Value of Drug Resistance Assays in Leukemia and Lymphoma, Amsterdam, 1992, provides a state-of-the-art discussion on drug resistance assays and their role in the design and individualization of treatment protocols.
Author: Ajay Vora
Publisher: Springer
ISBN: 3319397087
Category : Medical
Languages : en
Pages : 345
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Book Description
This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.
Author: Wojciech Gorczyca
Publisher: CRC Press
ISBN: 9781841845548
Category : Medical
Languages : en
Pages : 332
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Book Description
Effective treatment of the tumors of the hematopoietic system now often depends on an exact prognosis for the disorder concerned, and so the hematopathologist can give vital direction to the hematologic or oncologic clinician. Prognostic Markers in Hematologic Oncology comprehensively presents the numerous predictive and prognostic parameters in the practice of oncologic haematology and underlines their clinical relevance.
